fibrin and Intervertebral-Disc-Displacement

Back pain commonly arises from intervertebral disc (IVD) damage including annulus fibrosus (AF) defects and nucleus pulposus (NP) loss. Poor IVD healing motivates developing tissue engineering repair strategies. This study evaluated a composite injectable IVD biomaterial repair strategy using carboxymethylcellulose-methylcellulose (CMC-MC) and genipin-crosslinked fibrin (FibGen) that mimic NP and AF properties, respectively. Bovine ex vivo caudal IVDs were evaluated in cyclic compression-tension, torsion, and compression-to-failure tests to determine IVD biomechanical properties, height loss, and herniation risk following experimentally-induced severe herniation injury and discectomy (4 mm biopsy defect with 20% NP removed). FibGen with and without CMC-MC had failure strength similar to discectomy injury suggesting no increased risk compared to surgical procedures, yet no biomaterials improved axial or torsional biomechanical properties suggesting they were incapable of adequately restoring AF tension. FibGen had the largest failure strength and was further evaluated in additional discectomy injury models with varying AF defect types (2 mm biopsy, 4 mm cruciate, 4 mm biopsy) and NP removal volume (0%, 20%). All simulated discectomy defects significantly compromised failure strength and biomechanical properties. The 0% NP removal group had mean values of axial biomechanical properties closer to intact levels than defects with 20% NP removed but they were not statistically different and 0% NP removal also decreased failure strength. FibGen with and without CMC-MC failed at super-physiological stress levels above simulated discectomy suggesting repair with these tissue engineered biomaterials may perform better than discectomy alone, although restored biomechanical function may require additional healing with the potential application of these biomaterials as sealants and cell/drug delivery carriers.

Topics: Animals; Annulus Fibrosus; Biocompatible Materials; Biomechanical Phenomena; Carboxymethylcellulose Sodium; Cattle; Cross-Linking Reagents; Disease Models, Animal; Diskectomy; Fibrin; Hydrogels; In Vitro Techniques; Injections, Spinal; Intervertebral Disc Displacement; Iridoids; Materials Testing; Methylcellulose; Nucleus Pulposus

Minimally-invasive monitoring of regeneration in diseased tissue is an important aspect of stem cell therapy. Magnetic resonance imaging (MRI) based tracking of cells labelled with ferumoxides has the potential for non-invasive in vivo detection and longitudinal assessment of implanted cells. Cells labelled with ferumoxides appear as hypointense regions on MR images and thus can be distinguished from the surroundings. Application of this methodology to intervertebral disc degeneration (IVD), and detection of labelled cells implanted into the disc for tissue regeneration was examined. Mesenchymal stem cells labelled with a ferumoxide contrast agent were imaged in vitro to quantitatively characterize the signal intensity loss using MRI relaxation parameters (T1, T2, and T2*). To determine whether labelled cells could be detected within scaffolds suitable for implantation, labelled cells were seeded within both natural and synthetic polymers and imaged using MRI. Labelled cells were loaded within poly(ethylene glycol) hydrogels and imaged in vitro using both MRI and confocal microscopy. Labelled cells were also loaded into fibrin gels, and detected ex vivo within rat IVDs using MRI. Lastly, the effect of ferumoxide labelling on cell viability was investigated. Quantitatively, labelled cells demonstrate the greatest signal intensity loss and contrast on T2*-weighted images. Labelled cells can be detected in both synthetic and natural polymers, and can be distinguished from the native tissue environment of the rat IVD. Finally, labelling does not significantly impair cell viability. Consequently, this technique shows promise as a potential method for in vivo longitudinal tracking of stem cell based regeneration of the IVD.

Topics: Adult; Animals; Cell Survival; Cells, Cultured; Contrast Media; Dextrans; Ferrosoferric Oxide; Fibrin; Humans; Hydrogels; Intervertebral Disc; Intervertebral Disc Displacement; Iron; Magnetic Resonance Imaging; Magnetite Nanoparticles; Male; Mesenchymal Stem Cells; Oxides; Polyethylene Glycols; Rats; Regeneration; Staining and Labeling; Stem Cell Transplantation; Tissue Engineering

Topics: Animals; Arachnoiditis; Back Pain; Fibrin; Humans; Inflammation; Intervertebral Disc Displacement; Radiculopathy

Topics: Animals; Dog Diseases; Dogs; Fibrin; Intervertebral Disc Displacement; Ischemia; Necrosis; Spinal Cord; Syndrome